The interaction of plasma coagulation factors with membranes is a central phenomenon in hemostasis and thrombosis. Tissue factor is a lipoprotein component of many cell membranes and has the unique property of activating the extrinsic system of coagulation. It is the overall goal of this project to isolate and characterize tissue factor, to delineate its precise anatomical localization and to determine its mode of action. To date, it is clear that tissue factor interacts with coagulation factor VIII, forming a complex which proteolytically activates factor X. Themechanism by which tissue factor directs factor VII to activate factor X is under investigation. Another route by which coagulation maa be activated is via factor XII. This initiating reaction is mediated by collagen in a manner similar to the way in which tissue factor mediates the extrinsic system. This reaction is also being studied. The conversion of prothrombin to thrombin is catalyzed by activated factor X and markedly accelerated by factor V, phospholipids and calcium ions. This reaction is likely rate-limiting in coagulation and is thus probably and important step in physiological control. This reaction will be studied with regard to elucidating the stoichiometry of the reactants. Ultimately, the mechanism of action of the various accelerators will be studied. It is our hope that these studies will enable us to extend the current knowledge of the initiation, propagation and control of blood coagulation, hemostasis and thrombosis.